tbuckley/cabot-search huggingface dataset:
Comparative Effectiveness of an Artificial Air Pocket Device to Delay Asphyxiation in Supine Individuals Critically Buried in Avalanche Debris
Authors: Giacomo Strapazzon, Simon Rauch, Sandro Malacrida, Tomas Dal Cappello, Enrica Governo, Bruna Catuzzo, Simona Mrakic-Sposta, Margherita Urgesi, Marika Falla, Gianluca Cavoretto, Enrico Visetti, Guido Giardini, Hermann Brugger, Federico Prato
Journal: JAMA Network Open (2023)

Importance Approximately 70% of individuals critically buried in avalanche debris die within 35 minutes as a result of asphyxial cardiac arrest. An artificial air-pocket device (AAPD) that separates inhaled air from exhaled air may delay the onset of severe hypoxemia and eventual asphyxia during snow burial. Objective To investigate the efficacy of a new AAPD during snow burial in a supine position. Design, Setting, and Participants This comparative effectiveness trial was performed in winter 2016 with data analysis in November 2016 and November 2022. Each trial used a simulated critical avalanche burial scenario, in which a trough was dug in a snow pile and an additional air pocket of 0.5 L volume was punched into the lateral wall for each control trial. All participants were buried in a supine position. Trials could be voluntarily terminated at any time, with a maximum length of 60 minutes; trials were automatically terminated if the participant’s peripheral oxygen saturation (Sp o 2 ) dropped to less than 84%. Exposures Each participant conducted 2 trials, one in which they breathed into the AAPD (intervention trial) and the other in which they breathed into the prepared air pocket (control trial). Main Outcomes and Measures Measurements included Sp o 2 , cerebral oxygenation, ventilatory parameters, respiratory gas concentrations, and visual-analogue scales. Kaplan-Meier survival curves and rank test for matched survival data were used to analyze the total burial time in each trial. Results A total of 13 volunteers (9 men; mean [SD] age, 33 [8] years) were exposed to the intervention and control trials. Intervention trials were terminated less often (2 of 13 trials) as a result of hypoxemia than control trials (11 of 12 trials). Similarly, survival curves showed a longer duration of burial in the intervention compared with the control trials for the time to reach an Sp o 2 less than 84% (rank test for matched survival data: P = .003). The intervention trials, compared with the control trials, also had slower rates of decrease in fraction of inspired oxygen (mean [SD] rate, −0.8 [0.4] %/min vs −2.2 [1.2] %/min) and of increase in fraction of inspired carbon dioxide (mean [SD] rate, 0.5 [0.3] %/min vs 1.4 [0.6] %/min) and expired ventilation per minute (mean [SD] rate, 0.5 [1.0] L/min 2 vs 3.9 [2.6] L/min 2 ). Conclusions and Relevance This comparative effectiveness trial found that the new AAPD was associated with delaying the development of hypoxemia and hypercapnia in supine participants in a critical burial scenario. Use of the AAPD may allow a longer burial time before asphyxial cardiac arrest, which might allow longer times for successful rescue by companions or by prehospital emergency medical services.
The impact of the Covid-19 pandemic on postnatal depression: analysis of three population-based national maternity surveys in England (2014–2020)
Authors: Siân Harrison, Maria A. Quigley, Gracia Fellmeth, Alan Stein, Fiona Alderdice
Journal: The Lancet Regional Health - Europe (2023)

Few studies have evaluated postnatal depression before and during the Covid-19 pandemic using comparable data across time. We used data from three national maternity surveys in England to compare prevalence and risk factors for postnatal depression before and during the pandemic.Analysis was conducted using population-based surveys carried out in 2014 (n = 4571), 2018 (n = 4509), and 2020 (n = 4611). Weighted prevalence estimates for postnatal depression (EPDS score ≥13) were compared across surveys. Modified Poisson regression was used to estimate adjusted risk ratios (aRR) for the association between sociodemographic, pregnancy- and birth-related, and biopsychosocial factors, and postnatal depression.Prevalence of postnatal depression increased from 10.3% in 2014 to 16.0% in 2018 (difference = +5.7% (95% CI: 4.0-7.4); RR = 1.55 (95% CI: 1.36-1.77)) and to 23.9% in 2020 (difference = +7.9% (95% CI: 5.9-9.9); RR = 1.49 (95% CI: 1.34-1.66)). Having a long-term mental health problem (aRR range = 1.48-2.02), antenatal anxiety (aRR range = 1.73-2.12) and antenatal depression (aRR range = 1.44-2.24) were associated with increased risk of postnatal depression, whereas satisfaction with birth (aRR range = 0.89-0.92) and social support (aRR range = 0.73-0.78) were associated with decreased risk before and during the pandemic.This analysis indicates that Covid-19 had an important negative impact on postnatal women's mental health and may have accelerated an existing trend of increasing prevalence of postnatal depression. Risk factors for postnatal depression were consistent before and during the pandemic. Timely identification, intervention and follow-up are key to supporting women at risk, and it is essential that mechanisms to support women are strengthened during times of heightened risk such as the pandemic.NIHR Policy Research Programme.
Correction: Synaptic dysfunction of Aldh1a1 neurons in the ventral tegmental area causes impulsive behaviors
Authors: Xinyan Li, Wenting Chen, Xian Huang, Wei Jing, Tongmei Zhang, Quntao Yu, Hongyan Yu, Hao Li, Qing Tian, Yumei Ding, Youming Lu
Journal: Molecular Neurodegeneration (2023)
Phenome-wide analyses identify an association between the parent-of-origin effects dependent methylome and the rate of aging in humans
Authors: Chenhao Gao, Carmen Amador, Rosie M. Walker, Archie Campbell, Rebecca A. Madden, Mark J. Adams, Xiaomeng Bai, Ying Liu, Miaoxin Li, Caroline Hayward, David J. Porteous, Xueyi Shen, Kathryn L. Evans, Chris S. Haley, Andrew M. McIntosh, Pau Navarro, Yanni Zeng
Journal: Genome biology (2023)

Abstract Background The variation in the rate at which humans age may be rooted in early events acting through the genomic regions that are influenced by such events and subsequently are related to health phenotypes in later life. The parent-of-origin-effect (POE)-regulated methylome includes regions enriched for genetically controlled imprinting effects (the typical type of POE) and regions influenced by environmental effects associated with parents (the atypical POE). This part of the methylome is heavily influenced by early events, making it a potential route connecting early exposures, the epigenome, and aging. We aim to test the association of POE-CpGs with early and later exposures and subsequently with health-related phenotypes and adult aging. Results We perform a phenome-wide association analysis for the POE-influenced methylome using GS:SFHS ( N discovery = 5087, N replication = 4450). We identify and replicate 92 POE-CpG-phenotype associations. Most of the associations are contributed by the POE-CpGs belonging to the atypical class where the most strongly enriched associations are with aging (DNAmTL acceleration), intelligence, and parental (maternal) smoking exposure phenotypes. A proportion of the atypical POE-CpGs form co-methylation networks (modules) which are associated with these phenotypes, with one of the aging-associated modules displaying increased within-module methylation connectivity with age. The atypical POE-CpGs also display high levels of methylation heterogeneity, fast information loss with age, and a strong correlation with CpGs contained within epigenetic clocks. Conclusions These results identify the association between the atypical POE-influenced methylome and aging and provide new evidence for the “early development of origin” hypothesis for aging in humans.
Multi-label transcriptional classification of colorectal cancer reflects tumor cell population heterogeneity
Authors: Silvia Cascianelli, Chiara Barbera, Alexandra Ambra Ulla, Elena Grassi, Barbara Lupo, Diego Pasini, Andrea Bertotti, Livio Trusolino, Enzo Medico, Claudio Isella, Marco Masseroli
Journal: Genome Medicine (2023)

Transcriptional classification has been used to stratify colorectal cancer (CRC) into molecular subtypes with distinct biological and clinical features. However, it is not clear whether such subtypes represent discrete, mutually exclusive entities or molecular/phenotypic states with potential overlap. Therefore, we focused on the CRC Intrinsic Subtype (CRIS) classifier and evaluated whether assigning multiple CRIS subtypes to the same sample provides additional clinically and biologically relevant information.A multi-label version of the CRIS classifier (multiCRIS) was applied to newly generated RNA-seq profiles from 606 CRC patient-derived xenografts (PDXs), together with human CRC bulk and single-cell RNA-seq datasets. Biological and clinical associations of single- and multi-label CRIS were compared. Finally, a machine learning-based multi-label CRIS predictor (ML2CRIS) was developed for single-sample classification.Surprisingly, about half of the CRC cases could be significantly assigned to more than one CRIS subtype. Single-cell RNA-seq analysis revealed that multiple CRIS membership can be a consequence of the concomitant presence of cells of different CRIS class or, less frequently, of cells with hybrid phenotype. Multi-label assignments were found to improve prediction of CRC prognosis and response to treatment. Finally, the ML2CRIS classifier was validated for retaining the same biological and clinical associations also in the context of single-sample classification.These results show that CRIS subtypes retain their biological and clinical features even when concomitantly assigned to the same CRC sample. This approach could be potentially extended to other cancer types and classification systems.
Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy
Authors: Chuanming Liu, Wu Zuo, Guijun Yan, Shanshan Wang, Simin Sun, Shiyuan Li, Xinyi Tang, Yifan Li, Changjun Cai, Haiquan Wang, Wenwen Liu, Junshun Fang, Yang Zhang, Jidong Zhou, Xin Zhen, Tianxiang Feng, Yali Hu, Zhenbo Wang, Chaojun Li, Qian Bian, Haixiang Sun, Lijun Ding
Journal: Nature Aging (2023)
Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results
Authors: Andras Heczey, Xin Xu, Amy N. Courtney, Gengwen Tian, Gabriel A. Barragan, Linjie Guo, Claudia Martinez Amador, Nisha Ghatwai, Purva Rathi, Michael S. Wood, Yanchuan Li, Chunchao Zhang, Thorsten Demberg, Erica J. Di Pierro, Andrew C. Sher, Huimin Zhang, Birju Mehta, Sachin G. Thakkar, Bambi Grilley, Tao Wang, Brian D. Weiss, Antonino Montalbano, Meena Subramaniam, Chenling Xu, Chirag Sachar, Daniel K. Wells, Gianpietro Dotti, Leonid S. Metelitsa
Journal: Nature Medicine (2023)
Institutionalising community engagement for quality of care: moving beyond the rhetoric
Authors: Brynne Gilmore, Paul Henry Dsane-Aidoo, Mikey Rosato, Nuhu Omeiza Yaqub, Roseline Doe, Sushil Baral
Journal: BMJ (2023)

Community engagement has the potential to improve quality of care but is poorly represented in policy and the literature; its institutionalisation in health systems must be supported, argue <b>Brynne Gilmore and colleagues</b>
Antiviral therapy substantially reduces HCC risk in patients with chronic hepatitis B infection in the indeterminate phase
Authors: Daniel Q. Huang, Andrew Tran, Ming-Lun Yeh, Satoshi Yasuda, Pei-Chien Tsai, Chung-Feng Huang, Chia Yen Dai, Eiichi Ogawa, Masatoshi Ishigami, Takanori Ito, Ritsuzo Kozuka, Masaru Enomoto, Takanori Suzuki, Yoko Yoshimaru, Carmen M. Preda, Raluca I. Marin, Irina Sandra, Sally Tran, Sabrina X.Z. Quek, Htet Htet Toe Wai Khine, Norio Itokawa, Masanori Atsukawa, Haruki Uojima, Tsunamasa Watanabe, Hirokazu Takahashi, Kaori Inoue, Mayumi Maeda, Joseph K. Hoang, Lindsey Trinh, Scott Barnett, Ramsey Cheung, Seng Gee Lim, Huy N. Trinh, Wan-Long Chuang, Yasuhito Tanaka, Hidenori Toyoda, Ming-Lung Yu, Mindie H. Nguyen
Journal: Hepatology (2023)

HCC risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared with the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase.
Identification of an anergic BND cell–derived activated B cell population (BND2) in young-onset type 1 diabetes patients
Authors: Zachary C. Stensland, Christopher A. Magera, Hali Broncucia, Brittany D. Gomez, Nasha M. Rios-Guzman, Kristen L. Wells, Catherine A. Nicholas, Marynette Rihanek, Maya J. Hunter, Kevin P. Toole, Peter A. Gottlieb, Mia J. Smith
Journal: The Journal of Experimental Medicine (2023)

Recent evidence suggests a role for B cells in the pathogenesis of young-onset type 1 diabetes (T1D), wherein rapid progression occurs. However, little is known regarding the specificity, phenotype, and function of B cells in young-onset T1D. We performed a cross-sectional analysis comparing insulin-reactive to tetanus-reactive B cells in the blood of T1D and controls using mass cytometry. Unsupervised clustering revealed the existence of a highly activated B cell subset we term BND2 that falls within the previously defined anergic BND subset. We found a specific increase in the frequency of insulin-reactive BND2 cells in the blood of young-onset T1D donors, which was further enriched in the pancreatic lymph nodes of T1D donors. The frequency of insulin-binding BND2 cells correlated with anti-insulin autoantibody levels. We demonstrate BND2 cells are pre-plasma cells and can likely act as APCs to T cells. These findings identify an antigen-specific B cell subset that may play a role in the rapid progression of young-onset T1D.
Progression of liver disease and portal hypertension in dyskeratosis congenita and related telomere biology disorders
Authors: Anusha Vittal, Marena R. Niewisch, Sonia Bhala, Pujitha Kudaravalli, Farial Rahman, Julian Hercun, David E. Kleiner, Sharon A. Savage, Christopher Koh, Theo Heller, Neelam Giri
Journal: Hepatology (2023)

Dyskeratosis congenita (DC) and related telomere biology disorders (TBD) are characterized by very short telomeres and multisystem organ involvement including liver disease. Our study aimed to characterize baseline hepatic abnormalities in patients with DC/TBD and determine risk factors associated with liver disease progression.
Guardians of the oral barriers
Authors: Marcus Buggert
Journal: The Journal of Experimental Medicine (2023)

The oral mucosa serves as a frontline defense against many infections. Stolley et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20221853) discovered that the oral mucosa houses CD8+ CD103+ resident memory T cells, which are important for protecting against local viral infections in mice.
The emerging role of the gut mycobiome in liver diseases
Authors: Natalia Szóstak, Marek Figlerowicz, Anna Philips
Journal: Gut Microbes (2023)

In recent years, it has become clear that gut microbiota plays a major role in the human body, both in health and disease. Because of that, the gut microbiome and its impact on human well-being are getting wider and wider attention. Studies focused on the liver are not an exception. However, the majority of the analyses are concentrated on the bacterial part of the gut microbiota, while the fungi living in the human intestines are often omitted or underappreciated. This review is focused on the gut mycobiome as an important factor that should be taken into consideration regarding liver homeostasis and its perturbations. We have collected the findings in this field and we discuss their importance. We aim to emphasize the fungal compositional changes related to liver diseases and, by that, provide novel insights into the directions of liver research and gut microbiota as a therapeutic target for liver diseases.
Structural Ableism — Essential Steps for Abolishing Disability Injustice
Authors: Rupa Sheth Valdez, Bonnielin K. Swenor
Journal: New England Journal of Medicine (2023)

Interview with Ari Ne'eman on opportunities to support access to home- and community-based services for people with disabilities. (14:08)Download People with disabilities face inequities in social determinants of health, health care access and quality, and the impact of global crises, all of which compound the harms to the disability community.
Real-World Experience With Tofacitinib Dose De-Escalation in Patients With Moderate and Severe Ulcerative Colitis
Authors: Amy Yu, Nghiem B. Ha, Bingyan Shi, Yao-Wen Cheng, Uma Mahadevan, Kendall R. Beck
Journal: Clinical Gastroenterology and Hepatology (2023)

Tofacitinib is associated with sustained steroid-free remission in patients with ulcerative colitis (UC), with the lowest effective dose recommended for maintenance therapy. However, there are limited real-world data to guide decisions on the optimal maintenance regimen. We aimed to evaluate predictors and outcomes of disease activity after tofacitinib dose de-escalation in this population.Included were adults with moderate-severe UC treated with tofacitinib between June 2012 and January 2022. The primary outcome was evidence of UC disease activity-related events: hospitalization/surgery, corticosteroid initiation, tofacitinib dose increase, or therapy switch.Among 162 patients, 52% continued 10 mg twice daily while 48% underwent dose de-escalation to 5 mg twice daily. Cumulative incidence rates of UC events at 12 months were similar in patients with and without dose de-escalation (56% vs 58%; P = .81). In univariable Cox regression among patients with dose de-escalation, an induction course with 10 mg twice daily for more than 16 weeks was protective of UC events (hazard ratio [HR], 0.37; 95% CI, 0.16-0.85) while ongoing severe disease (Mayo 3) was associated with UC events (HR, 6.41; 95% 95% CI, 2.23-18.44), which remained significant after adjusting for age, sex, duration of induction course, and corticosteroid use at dose de-escalation (HR, 6.05; 95% CI, 2.00-18.35). Twenty-nine percent of patients with UC events had their dose re-escalated to 10 mg twice daily, with only 63% able to recapture clinical response at 12 months.In this real-world cohort, we observed a 56% cumulative incidence of UC events at 12 months in patients with tofacitinib dose de-escalation. Observed factors associated with UC events after dose de-escalation included induction course for fewer than 16 weeks and active endoscopic disease 6 months after initiation.
Ultrasensitive <scp>NGS MRD</scp> assessment in Ph+ <scp>ALL</scp>: Prognostic impact and correlation with <scp>RT‐PCR</scp> for <i>BCR::ABL1</i>
Authors: Nicholas J. Short, Elias Jabbour, Walid Macaron, Farhad Ravandi, Nitin Jain, Rashmi Kanagal‐Shamanna, Keyur P. Patel, Sanam Loghavi, Fadi G. Haddad, Musa Yilmaz, Ghayas C. Issa, Partow Kebriaei, Steven M. Kornblau, Sarah Pelletier, Wilmer Flores, Jairo Matthews, Rebecca Garris, Hagop Kantarjian
Journal: American Journal of Hematology (2023)

Reverse transcription polymerase chain reaction (RT-PCR) for BCR::ABL1 is the most common and widely accepted method of measurable residual disease (MRD) assessment in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL); however, RT-PCR may not be an optimal measure of MRD in many cases of Ph+ ALL. We evaluated the clinical impact of a highly sensitive next-generation sequencing (NGS) MRD assay (sensitivity of 10-6 ) and its correlation with RT-PCR for BCR::ABL1 in patients with Ph+ ALL. Overall, 32% of patients had a discordance between MRD assessment by RT-PCR and NGS, and 31% of patients who achieved NGS MRD negativity were PCR+ at the same timepoint. Among eight patients with long-term detectable BCR::ABL1 by PCR, six were PCR+/NGS-. These patients generally had stable PCR levels that persisted despite therapeutic interventions, and none subsequently relapsed; in contrast, patients who were PCR+/NGS+ had more variable PCR values that responded to therapeutic intervention. In a separate cohort of prospectively collected clinical samples, 11 of 65 patients (17%) with Ph+ ALL who achieved NGS MRD negativity had detectable BCR::ABL1 by PCR, and none of these patients relapsed. Relapse-free survival and overall survival were similar in patients who were PCR+/NGS- and PCR-/NGS-, suggesting that PCR for BCR::ABL1 did not provide additional prognostic information in patients who achieved NGS MRD negativity. NGS-based assessment of MRD is prognostic in Ph+ ALL and identifies patients with low-level detectable BCR::ABL1 who are unlikely to relapse nor to benefit from therapeutic interventions.
Correction: Distinct Cell Adhesion Signature Defines Glioblastoma Myeloid-Derived Suppressor Cell Subsets
Authors: Defne Bayik, Cynthia F. Bartels, Katreya Lovrenert, Dionysios C. Watson, Duo Zhang, Kristen Kay, Juyeun Lee, Adam Lauko, Sadie Johnson, Alice Lo, Daniel J. Silver, Mary McGraw, Matthew Grabowski, Alireza M. Mohammadi, Filippo Veglia, Yi Fan, Michael A. Vogelbaum, Peter Scacheri, Justin D. Lathia
Journal: Cancer Research (2023)

In the original version of this article (1), there were errors in Fig. 6. Specifically, the datapoints in the left half of Fig. 6F representing vehicle- and sitagliptin-treated mMDSCs were also used in the right half of Fig. 6F representing vehicle- and sitagliptin-treated gMDSCs and in Fig. 6E. The correct graphs for Fig. 6E and 6F have been provided, and the text has been updated to indicate the difference in Fig. 6E was not significant. The errors have been corrected in the latest online HTML and PDF versions of the article. The authors regret these errors.
Are endothelial cell proliferation and mesenchymal transition as distinguishing characteristics of 3-week Sugen5416/hypoxia mice model?
Authors: Ruixuan Zheng, Tingting Xu, Ya Lin, Xiaoying Huang
Journal: Cardiovascular Research (2023)

Figure 1 (A) DEGs of endothelial cell proliferation (GO:0001935).Control group vs. SuHx group: three control groups, respectively, include 4935, 3429, and 3209 cells, and three SuHx groups, respectively, include 5127, 5805, and 2997 cells.(B) Expression level of ACTA2 in CDH5(+) and PECAM(+) cells.Three control groups, respectively, include 1875, 2020, and 1056 CDH5(+) and PECAM(+) cells and three IH groups, respectively, include 3084, 2075, and 2104 CDH5(+) and PECAM(+) cells.Significant difference tested by FindMarkers function of Seurat, Wilcox method was used for differential expression analysis, and both min.pctand logfc.thresholdwere set as 0.2.(C ) Expression proportion of ACTA2 in CDH5(+) and PECAM(+) cells.Control group vs. IH group: three control groups, respectively, include 478, 607, and 183 ACTA2(+) cells and three IH groups, respectively, include 819, 697, and 434 ACTA2(+) cells.Not significant test by unpaired t-test (P = 0.55).(D) Representative images of immunofluorescence double-stained of PECAM and ACTA2 in lung cryo-sections from mice under normoxia and three-week SuHx.